Medicament and a method for regulation of the vascular tone

ABSTRACT

The antibody based medicament contains ultra low doses of monoclonal, polyclonal, immune or natural antibodies to a protein or a peptide involved in the vascular tone regulation or mediating the effects of other regulators; these antibodies are used in activated (potentiated) form produced by multiple subsequent dilution and external impact, preferably in accordance with homeopathic technology. The method of treatment for diseases accompanied by disturbances of the vascular tone utilizes the use of ultra low doses of antibodies to a protein or a peptide involved in the vascular tone regulation or mediating the effects of other regulators; these antibodies are used in activated form produced by multiple subsequent dilution and external impact.

The invention belongs to the field of medicine and can be utilized tonormalize the vascular tone and prevent acute and chronic illnessesaccompanied by disturbances of the vascular tone, primarily in thearteries.

The prior art includes use of antibodies in the treatment ofpathological syndromes (SU 1331508 A, A 61 K 39/00, 1984; SU 1730144 A1,C 12 N 7/00, 1992).

Medications such as sera and immunoglobulins based on antibodies intherapeutic concentrations, have also been described (e.g., see“Register of remedies used in Russia. The encyclopaedia of remedies”,7^(th) edition, 2000, pp. 358-359 (in Russian)).

None of the mentioned medications, however, are used in the treatment ofdiseases characterized by disturbances of the vascular tone.

There has been described a method of treating diseases accompanied bydisturbances of the vascular tone through administration of substancesspecifically interacting with endogenous factors involved in thevascular tone regulation (e.g., see “Register of remedies used inRussia. The encyclopaedia of remedies”, 7^(th) edition, Moscow, RLS,2000, pp. 178, 406 (in Russian)). The most important disadvantage ofsuch medications is their adverse effects.

The invention is aimed at producing an effective and safe medicament fortreatment and prevention of diseases accompanied by disturbances of thevascular tone (primarily in the arteries), wherein activated(potentiated) antibodies are used.

This task is solved by the presence in the medicament of ultra low dosesof monoclonal, polyclonal, immune or natural antibodies to a protein ora peptide involved in the vascular tone regulation or mediating theeffects of other regulators; these antibodies are used in activated(potentiated) form produced by multiple subsequent dilution and externalimpact, primarily in accordance with homeopathic technology.

The method of treatment for diseases accompanied by disturbances of thevascular tone, primarily in the arteries, presents the use of antibodiesto a protein or a peptide involved in the vascular tone regulation ormediating the effects of other regulators; these antibodies are used inactivated form produced by multiple subsequent dilution and externalimpact.

The use of a mixture of different, preferably centesimal, homeopathicdilutions is most beneficial.

Experiments have been carried out to prove that the administeredactivated (potentiated) antibodies to a protein or a peptide involved inthe vascular tone regulation exert a modifying, instead of inhibiting,effect on physiological and pathological processes mediated or regulatedby this protein or peptide; the latter is responsible for thetherapeutic efficiency of the medication presented.

The medication produced in accordance with the invention presents a newpharmacological preparation characterized by the presence of specificpharmacological activity, the absence of adverse effects as well as drugtolerance and dependence; by ecological purity and a low prime cost.

The drug preparation is produced as follows.

To treat a disease or a pathological syndrome caused or accompanied bydisturbances of the vascular tone, clinical experiments are used todiscover a protein or peptide regulating the vascular tone, whichalterations characterize this disease or accompany its development.

Biochemical methods are used to separate this peptide or protein.Thereafter, the whole protein or its fragment (not less than 3aminoacids) is utilized as an immunogen in the immunization oflaboratory animals and producing immune antibodies, or in ahybridizomatechnology to produce monoclonal antibodies. The antibodiesproduced are purified by affinity chromatography.

The technique of immune and monoclonal antibody production is described,for example, in: Immunological methods (Ed. by H. Friemel), Moscow,Medicine publishers, 1987, pp. 9-23 (book in Russian).

Multiple subsequent dilutions and external impact, usually mechanical,are exerted on the isolated antibodies until ultra low or low doses areproduced, e.g., preferably in accordance with homeopathic technology ofpotentiation (dynaniization) (see V. Shvabe, Homeopathic PharmaceuticalAgents. A Manual on Description and Preparation, Moscow, 1967, p.12-38). (in Russian)). To do so, a uniform concentration reduction isemployed wherein 1 volume unit of the antibodies is diluted in 9 volumeunits (for a decimal dilution D) or in 99 volume units (for a centesimaldilution C) of a neutral diluent with multiple vertical shaking of everydilution; for the most part, separate containers are used for everysubsequent dilution until the needed concentration (potency) is reached.

External impacts in the concentration reduction process can also includeultrasound, electromagnetic or other physical influences.

The medication thus prepared is utilized preferably in commonhomeopathic dosage forms and dilutions, in alcohol or aqueous solutionsor tablets (granules) prepared by impregnation until saturation of theexcipient with a potentiated solution or by direct instillation of thelatter into a liquid dosage form. To enhance the therapeutic effect ofthe preparation, a mixture of different homeopathic dilutions isemployed.

EXAMPLES Example 1

An experimental study was performed to evaluate the effect of antibodiesto angiotensin II receptor (Anti-R-angiotensin-II-c), activated forms ofultra low doses, on blood pressure in ISIAH strain rats with hereditaryarterial hypertension. Blood pressure in the caudal artery was measuredafter 5 days of peroral administration of potentiated polyclonal rabbitantibodies against the C-terminal fragment of the human angiotensin IIreceptor, antibodies being employed in a mixture of homeopathicdilutions C12+C30+C200 (0.5 ml of water solution).

The blood pressure figures before and after drug administration arepresented in Table 1.

TABLE 1 Effect of Anti-R-angiotensin-II-c on blood pressure inhypertensive ISIAH strain rats. Blood Blood Blood pressure afterpressure after Baseline pressure Decrease subsequent Increase secondDecrease blood pressure after in blood 7 days in blood 5-day in blood(average of 3 5 days of pressure without pressure treatment pressure #Rat # measurements) treatment (3) − (4) medication (6) − (4) course (6)− (8) 1 2 3 4 5 6 7 8 9 1 31 175 151 24 166 15 150 16 2 32 184 163 21186 23 170 16 3 33 186 169 17 165 −4 150 15 4 4 171 165 6 189 24 170 195 34 187 172 15 190 18 175 15 6 10 181 166 15 185 19 170 15 7 11 171 1629 169 7 155 14 8 38 182 160 22 185 25 165 20 9 16 180 169 11 183 14 16518 10 19 186 166 20 186 20 170 16 X ± m 180 ± 1.91 164 ± 1.86 16 ± 1.88180 ± 3.08 16.1 ± 2.81 164 ± 2.87 16.4 ± 0.62

The data in the table show that the medication exerts a hypotensiveeffect.

Example 2

An experimental study was performed to evaluate the effect of antibodiesto angiotensin II (activated forms of ultra low doses) on blood pressurein ISIAH strain rats with hereditary arterial hypertension. Bloodpressure in the caudal artery was measured after 5 days of peroraladministration of potentiated monoclonal antibodies to angiotensin IIemployed in a mixture of homeopathic dilutions C12+C30+C200 (0.5 ml ofwater solution).

The blood pressure figures before and after drug administration aregiven in Table 2.

TABLE 2 Blood Change in pressure Change in blood blood pressure BaselineBlood pressure after pressure after a after 5 days of blood 3 hoursafter a 5 days of single shot ((3) − treatment ((4) − Rat # pressuresingle shot treatment (2) difference) (2) difference) 1 2 3 4 5 6 11 200167 161 −33 −39 12 189 150 189 −39 0.0 16 200 189 160 −11 −40 19 167 178144 11 −23 21 211 189 167 −22 −44 22 178 167 205 −11 27 23 189 167 205−22 16 27 178 194 200 16 22 28 178 172 144 −6 −34 30 189 178 178 −11 −11Mean ± 187.9 ± 4.16 175.1 ± 4.21 175.3 ± 7.48 −12.8* ± 5.49 −12.6 ± 8.65SEM *(p < 0.05)

The data in this table present a pronounced hypotensive effect of themedication.

Example 3

An experimental study was performed to evaluate the effect of antibodiesto angiotensin I (activated forms of ultra low doses) on blood pressurein ISIAH strain rats with hereditary arterial hypertension. Bloodpressure in the caudal artery was measured after 5 days of peroraladministration of potentiated polyclonal mouse antibodies to angiotensinI employed in a mixture of homeopathic dilutions D6+C12+C200 (0.5 ml ofwater solution).

The blood pressure figures before and after drug administration arepresented in Table 3.

TABLE 3 Change in blood Blood Change in pressure after Blood pressureblood pressure 5 days of Baseline pressure 3 after after a singletreatment blood hours after a 5 days of dose ((3) − (2) ((4) − (2)Parameter pressure single dose treatment difference) difference) Mean ±189.0 ± 4.1 178.1 ± 5.3 175.8 ± 8.2 −10.9* ± 5.9 −13.2 ± 8.5 SEM *(p <0.05)

The data in the table show that the medication exerts a hypotensiveeffect.

Example 4

Patient D., 50 years old, presented with a 10-year history of essentialhypertension. On clinical and instrumental examination, he was diagnosedwith “essential hypertension with primary heart involvement, 2^(nd)degree, myocardial hypertrophy of the left ventricle”. He wasadministered polyclonal rabbit antibodies against the C-terminalfragment of the angiotensin II receptor (a mixture of homeopathicdilutions C12+C30+C200), 1 tablet BID. The blood pressure stabilized at130-135/85 mm Hg within 7 days of the start of treatment. After 2 monthsof treatment, electrocardiography revealed a decrease in the myocardialhypertrophy and overload of the left ventricle.

Example 5

Patient Z., 50 years old, had a 10-year history of essentialhypertension with primary kidney involvement. Prior to the start ofantihypertensive treatment, her blood pressure was as high as 180/110 mmHg. On clinical interview, she complained of headaches, edema, andfatigue. After the conventional antihypertensive measures had proved tobe ineffective, she was administered monoclonal antibodies against theangiotensin II receptor (a mixture of homeopathic dilutionsC12+C30+C200) and monoclonal antibodies against angiotensin II (amixture of homeopathic dilutions D12+C30+LM2), 1 tablet BID. After 7days of treatment, the patient reported an increase in energy levels,subsidence of the edema, and a stable blood pressure decrease to 140/95mm Hg. After 2 months of treatment, blood pressure levels stabilized at130/90 mm Hg, proteinuria went down from 0.3 g/l to 0.06 g/1.

Example 6

Patient V., 42 years old, had suffered from moderate Cushing's diseasefor 5 years. To treat her pronounced hypertension (up to 175/100 mm Hg),she was administered a compound preparation containing the following:polyclonal rabbit antibodies against the angiotensin II receptor (amixture of homeopathic dilutions C12+C30+C200) and monoclonal antibodiesagainst adrenocorticotropin (a mixture of homeopathic dilutionsC12+C30±C200), 1 tablet TID. After 2 weeks of treatment, her bloodpressure fell to 140/90 mm Hg, she was generally feeling better. After 1month of treatment, serum ACTH levels decreased from 200 to 130 pg/ml,the body mass index went down from 37 to 35 kg/m². The patient wasadvised to go on with the treatment.

Example 7

Patient N., 52 years, diagnosed with “coronary artery disease, angina ofeffort, functional class 3; peripheral atherosclerotic disease of thelower extremities”. This patient was administered activated polyclonalrabbit antibodies against the C-terminal fragment of human endothelialNO synthase (type III nitrogen oxide synthase) as a monotherapy, in amixture of homeopathic dilutions C12+C30+C200, 1 tablet 3 TID, After 7days of treatment, the patient noticed an improvement in exercisetolerance and general health. Pain in the lower extremities on fastwalking appeared within 30 to 40 minutes (instead of 10 to 15 minutesprior to treatment). After 3 weeks of treatment, ECO showed animprovement in left ventricular myocardial ischemia and class 2 anginaof effort.

Example 8

Patient O., 67 years old, suffered from hypertension and decompensatedtype II diabetes mellitus. She had been having heart failure symptoms(cardiac asthma, congestive rales in the lungs) for 2 years andperipheral edema in the lower extremities for 2 months. In view ofinefficiency of conventional treatment, she was administered a compoundincluding activated monoclonal antibodies against tumor necrosis factoralpha (TNF-α) (a mixture of homeopathic dilutions C12+C30+C200) andactivated antibodies against the TNF-α receptor (a mixture ofhomeopathic dilutions D12+LM10), 1 tablet BID. After 10 days oftreatment, the heart failure improved, the peripheral edema was gone,there were no signs of pulmonary congestion, the patient was feelingbetter. The insulin dosage enough to control glycemia fell from 40 to 20IU per day.

Example 9

Patient D., 62 years old, suffered from circulatory encephalopathy clueto atherosclerosis with predominant involvement of the cerebralarteries. He had a history of multiple transient ischemic attacks (TIAs)and presented with an on-going attack accompanied by right-sidehemiparesis and aphasia. The patient was given polyclonal antibodiesagainst endothelial nitrogen oxide synthase (a mixture of homeopathicdilutions C12+C30+C200), 1 tablet dissolvable in the mouth every 30minutes. After 4 hours of treatment, TIA symptoms (vertigo, tinnitus,weakness in the right arm, aphasia) showed signs of subsidence. Within12 hours of the start of treatment, the attack was completely overcome.

Example 10

Patient M., 32 years old, had Raynaud's phenomenon secondary to aconnective tissue disorder. Because of the worsening condition, she wasadministered monoclonal antibodies against endothelial nitrogen oxidesynthase (a mixture of homeopathic dilutions C12+C30+C200), 1 tabletTID. After 7 days of treatment, the patient noticed that attacksprecipitated by exposure of the extremities to cold had become lessfrequent, less painful and shorter. The patient was advised to continuethe treatment.

Example 11

Patient V., 19 years old. She was evaluated for headaches and vertigoand diagnosed with hypotensive neurocirculatory asthenia (blood pressure80/60 mm Hg). The patient was administered monoclonal antibodies againstangiotensin I (a mixture of homeopathic dilutions C12+C30+C200) combinedwith activated angiotensin 1 (a mixture of homeopathic dilutionsC12+C30+C200), 1 tablet TID. After 2 weeks of treatment, blood pressurestabilized at 100/80 mm Hg, the headaches had subsided and become lessfrequent.

Example 12

Patient O., 42 years old. On examination at the Labour Medicine ResearchInstitute, he was diagnosed with vibration disease, 2^(nd) stagelocalized variant. Due to the angiospastic syndrome accompanied byvegetosensory polyneuropathy and skin atrophy, which was resistant toconventional treatment, the patient was administered polyclonal rabbitantibodies against endothelin-1 (a mixture of homeopathic dilutionsC12+C30+C200) combined with monoclonal antibodies against bradykinin (amixture of homeopathic dilutions D6+C30+LM2), 1 tablet TID. After 10clays of treatment, the angiospastic syndrome improved, which was alsoshown on capillaroscopy. After 2 months of treatment, the polyneuropathyand skin atrophy significantly subsided. The patient was advised tocontinue the treatment.

1. A medicament comprising a homeopathically potentized form of at least one antibody to angiotensin receptor.
 2. The medicament of claim 1 wherein said antibody is selected from monoclonal, polyclonal or natural antibodies.
 3. The medicament of claim 1 wherein said antibody to angiotensin receptor is to the angiotensin II receptor.
 4. The medicament of claim 1 wherein said antibody to angiotensin receptor is to angiotensin I receptor.
 5. The medicament of claim 1 wherein said antibody to angiotensin receptor is to the C-terminal fragment of the angiotensin II receptor.
 6. The medicament of claim 1, wherein said homeopathically potentized form comprises one or more homeopathic dilutions.
 7. The medicament of claim 6, wherein said one or more homeopathic dilutions comprises one or more centesimal homeopathic dilutions.
 8. The medicament of claim 6, wherein said one or more homeopathic dilutions comprises C12, C30, and C200 homeopathic dilutions.
 9. The medicament of claim 6, wherein said one or more homeopathic dilutions comprises D6, C12, and C200 homeopathic dilutions. 